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Effects of T-helper 2-type cytokines, interleukin-3 (IL-3), IL-4, IL-5, and
IL-6 on the survival of cultured human mast cells
M Yanagida, H Fukamachi, K Ohgami, T Kuwaki, H Ishii, H Uzumaki, K Amano, T Tokiwa, H Mitsui and H Saito
Pharmaceutical Development Laboratory, Kirin Brewery Co, Ltd, Gunma, Japan.
Although stem cell factor (SCF) has been identified as a critical cytokine
for the development of human mast cells from their progenitors, the effects
of other cytokines on human mast cells are less well understood. We
examined the effects of several cytokines on the survival of human mast
cells of 100% purity generated in suspension cultures of umbilical cord
blood mononuclear cells in the presence of 100 ng/mL recombinant human (rh)
SCF and interleukin-6 (IL-6). Mast cells suspended in conventional
serum-containing medium died over a period of 2 to 6 days after the
withdrawal of SCF and IL-6. The cells became pyknotic and underwent DNA
fragmentation characteristic of apoptosis. The addition of SCF, IL-3, IL-4,
IL-5, or IL-6 to the cultures in both serum-containing and serum-free
medium prolonged their survival in a dose-dependent manner. Some other
cytokines, such as IL- 2, IL-9, IL-10, IL-11, tumor necrosis factor-alpha,
transforming growth factor-beta 1, and nerve growth factor, had no
survival-promoting effect at 100 ng/mL. Preincubation of mast cells with
SCF, IL-4, IL-5, or IL-6 for 24 hours during sensitization with IgE
enhanced IgE/anti- IgE antibody-induced histamine release from mast cells,
whereas IL-3 showed a negligible effect. Polymerase chain reaction
amplification of alpha-chains of IL-3 receptor (R), IL-4 R, IL-5 R, and
IL-6 R yielded products of the correct size predicted from the sequence of
each receptor. The binding assay using 125I-labeled IL-3 indicated that
these mast cells bear receptors for IL-3. These findings suggest that IL-3,
Il-4, IL-5, and IL-6, which are mainly produced by T-helper 2 lymphocytes,
might regulate the functions of human mast cells in vivo via specific
receptors in allergic reactions.
Volume 86,
Issue 10,
pp. 3705-3714,
11/15/1995
Copyright © 1995 by The American Society of Hematology
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